Principles which govern conformation, surface recognition and function of peptides and proteins have been studied for neurophysin-neuropeptide hormone complexes and their precursors as well as for several other advantages peptides and proteins. Molecular recognition by peptides and proteins underlies essentially all biological functions of these substances, emphasizing the importance of understanding surface organization and dynamics in defining structural bases of function. This issue has been addressed for the neurohypophysial hormones oxytocin and vasopressin and associated neurophysins, which form cooperative peptide-protein complexes that act as storage forms for the polypeptides in neurosecretroy granules. The nature and structural interrelationships between the self-association and hormone binding surfaces in neurphysins that give rise to cooperative complexes (marked by quaternary enhancement) have been studied. Methods for analytical high performance affinity chromatography are being developed for the evaluation of these interactions for molecular species isolated both from various neuroendocrine sites and by vitro sequence modification. Neurophysin isoforms of related but variant sequences have been identified and shown to have similar hormonal recognition properties in spite of sequence changes. Separately, the concept of interdependence between structural framework and surface recognition of peptides and proteins has been evaluated by studing the effect of synthetic sequence modeling of ribonuclease S-peptide on formation of functional ribonuclease-S. The structure of a modeled semisynthetic robonuclease-S is being solved to high resolution by X-ray diffraction analysis . In addition, the way in which intramolecular domains participate in folding and stabilization continues to be evaluated in a study of large, C-terminal-derived, fragments of thermolysin. A role is suggested for domains in forming intramolecular inter-domain surface contacts to stabilize overall native protein structure. The role of domains in protein folding per se is being evaluated.